rs10488596

Variant names:

• chr7-136873847-C-T
• rs10488596
• NM_001006630.2:c.-125+4429C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001006630.2(CHRM2):​c.-125+4429C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,188 control chromosomes in the GnomAD database, including 1,475 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1475 hom., cov: 33)
• Consequence: CHRM2 NM_001006630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549
• Publications: 3 publications found

Genes affected

CHRM2 (HGNC:1951): (cholinergic receptor muscarinic 2) The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine to these receptors and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The muscarinic cholinergic receptor 2 is involved in mediation of bradycardia and a decrease in cardiac contractility. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

ENSG00000234352 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRM2	NM_001006630.2	c.-125+4429C>T		intron_variant	Intron 2 of 3	ENST00000680005.1	NP_001006631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRM2	ENST00000680005.1	c.-125+4429C>T		intron_variant	Intron 2 of 3		NM_001006630.2	ENSP00000505686.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20025 AN: 152072 Hom.: 1476 Cov.: 33

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.130

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.132 AC: 20019 AN: 152188 Hom.: 1475 Cov.: 33 AF XY: 0.128 AC XY: 9554 AN XY: 74406

African (AFR) AF: 0.0814 AC: 3382 AN: 41554

American (AMR) AF: 0.123 AC: 1875 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3470

East Asian (EAS) AF: 0.0114 AC: 59 AN: 5178

South Asian (SAS) AF: 0.0891 AC: 430 AN: 4826

European-Finnish (FIN) AF: 0.153 AC: 1622 AN: 10580

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.173 AC: 11765 AN: 67980

Other (OTH) AF: 0.128 AC: 271 AN: 2110

Alfa AF: 0.157 Hom.: 1150

Bravo AF: 0.126

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.42
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10488596; hg19: chr7-136558594;